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Protocol Details

A Phase 1b/2 Trial of Hu5F9-G4 in Combination with Rituximab or Rituximab + Chemotherapy in Patients with Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Monoclonal Antibody;

Recruitment Keyword(s)



Non-Hodgkin Lymphoma;
Large B-Cell;
Diffuse Indolent Lymphoma

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: Rituximab
Biological/Vaccine: Magrolimab
Drug: Gemcitabine
Drug: Oxaliplatin

Supporting Site

National Cancer Institute


The antibody Hu5F9-G4 blocks the protein CD47. Cancer cells use this protein to protect themselves from the body s immune system. The drug rituximab is a standard treatment for non-Hodgkin s lymphoma. Researchers want to see if giving the antibody and the drug together can fight the cancer.


To test the safety of Hu5F9-G4 given with rituximab in people with non-Hodgkin s lymphoma. To learn the best dose, side effects, and if it reduces cancer growth.


Adults ages 18 and older who have indolent lymphoma or Diffuse Large B Cell lymphoma that not responded to previous treatments.


Participants will be screened with:

-Medical history

-Physical exam

-Vision test

-Blood and urine tests

-Heart test

-Removing a small piece of tumor

-Imaging studies to look at the tumor

-Some participants will have a sample of bone marrow taken.

Treatment will be in 4-week cycles as long as the participant tolerates it and the cancer does not worsen.

For each cycle, participants will:

-Repeat most of the screening tests

-Have blood taken several times

-Get Hu5F9-G4 each week by needle inserted in a vein for about 2 hours. In cycle 1, they will also get a dose on day 1 for about 3 hours.

-Get rituximab by needle inserted in a vein. They will get it weekly in cycle 1. For cycles 2-6 they will get it on day 1 only. They will not get it after cycle 6.

After ending treatment, participants will have a follow-up visit within 30 days. They will repeat some screening tests. They will be contacted every few months for about 5 years.

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1. Adults greater than or equal to 18 years

2. Antibody combination (magrolimab + rituximab) Phase 1b cohort only: B-cell NHL expressing CD20 by immunohistochemistry (IHC) or flow cytometry, relapsed or refractory to at least 2 prior lines of therapy

3. DLBCL chemotherapy combination (magrolimab + R-GemOx) Phase 1b safety dose-escalation and expansion cohorts:

a. Histologically confirmed de novo or transformed DLBCL relapsed or refractory to 1 to 3 prior lines of therapy who are not candidates for highdose chemotherapy and autologous stem cell transplantation (ASCT). Patients relapsed after ASCT are allowed.

b. At least 1 prior therapy must have included a CD20-targeted therapy.

c. Primary refractory patients are excluded as defined by failure to achieve a partial response (PR) or complete response (CR) to frontline therapy or progression within 3 months of completing treatment.

d. The 1 to 3 prior lines of therapy requirement is only applicable for

treatment regimens for DLBCL and not for prior lymphomas in the case of transformed DLBCL.

4. For the DLBCL antibody combination (magrolimab + rituximab) Phase 2 Cohort 4, de novo or transformed DLBCL, not otherwise specified, according to the World Health Organization 2016 classification of lymphoid neoplasms (Swerdlow 2016) expressing CD20 by IHC or flow cytometry, that is relapsed or refractory to at least 2 prior lines of therapy containing and anti-CD20 therapy. Prior autologous hematopoietic cell transplantation is permitted.

5. Indolent lymphoma Phase 2 cohort: Histologically confirmed marginal zone or follicular lymphoma (Grade 1-3a) expressing CD20 by IHC or flow cytometry, relapsed or refractory to at least 2 prior lines of therapy

6. Eastern Cooperative Oncology Group (ECOG) score 0-2

7. Disease that is measurable or assessable for response per Lugano Classification for lymphomas

8. Laboratory measurements, blood counts:

-- Hemoglobin must be >= 9 g/dL within 24 hours prior to the first 2 doses of magrolimab infusion. NOTE: Transfusions are allowed to meet hemoglobin eligibility

-- Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10^9/mL

--For the antibody combination (magrolimab + rituximab) Phase 1b and Phase 2 cohorts: Platelets greater than or equal to 50 (SqrRoot) 109/mL

--For the Phase 1b chemotherapy combination (magrolimab + R-GemOx) safety dose-escalation and expansion cohorts only, platelets

greater than or equal to 100 (SqrRoot) 109/mL

9. Laboratory measurements, hepatic function:

-- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 5 times upper limit of normal (ULN)

-- Bilirubin less than or equal to 1.5 x or 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert s syndrome or a genetic equivalent

10. Laboratory measurements, renal function:

-- Serum creatinine less than or equal to 1.5 x ULN or calculated glomerular filtration rate (GFR) greater than 40 mL/min/1.73 m^2

11. Women of childbearing potential (WOCBP) must not be nursing or planning to be pregnant and must have a negative urine or serum pregnancy test within 30 days before enrollment and within 72 hours before the first administration of magrolimab.

12. WOCBP must be willing to use at least 1 highly effective method of contraception during the study and continue for 4 months after the last dose of magrolimab and 12 months after the last dose of rituximab

13. Male patients who are sexually active with a WOCBP and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation during the study and for 4 months after the last dose of magrolimab and 12 months after the last dose of rituximab. If the partner is pregnant, male patients must use barrier method contraception (condom) during the study and for 4 months after the last dose of magrolimab and until there is a pregnancy outcome (whichever is applicable) to prevent fetal exposure to study drugs.

14. Patient has provided informed consent

15. Must be willing and able to comply with clinic visits and procedures outlined in the study protocol

16. DLBCL chemotherapy combination (magrolimab + R-GemOx) Phase 1b safety dose-escalation and expansion cohorts and Phase 2 antibody combination (magrolimab + rituximab) indolent lymphoma and DLBCL cohorts only: Willing to consent to 1 mandatory pretreatment and 1 on-treatment tumor biopsy, unless determined to not be feasible by the Investigator (Reasons include, but are not limited to, lack of accessible tumor tissue to biopsy and patient safety


17. CAR-T na(SqrRoot) ve or CAR-T ineligible patients and otherwise meet other inclusion/exclusion criteria may enroll. Patients who relapse following CAR-T therapy are not eligible.


1. Patients with active brain metastases. (Patients with stable treated central nervous system (CNS) lesions who are off corticosteroid therapy for at least 3 weeks are not considered active.)

2. Prior allogeneic stem cell transplant

3. Prior anti-cancer therapy including chemotherapy, hormonal therapy, or investigational agents within 3 weeks or within at least 4 half-lives prior to magrolimab dosing (up to a maximum of 4 weeks), whichever is longer.

NOTE: Low dose steroids (oral prednisone or equivalent less than or equal to 20 mg per day), localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion.

4. Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV).

5. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening. RBC transfusions are permitted during screening and prior to enrollment to meet the hemoglobin inclusion criteria.

6. History of hemolytic anemia or Evans syndrome in the last 3 months.

7.Positive IgG component of the direct antiglobulin test (DAT).

8. Prior treatment with CD47 or signal regulatory protein alpha (SIRP-alpha) targeting agents.

9. Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancy for which patients are not on active anti-cancer therapy as defined in Exclusion Criterion 2.

10. Hypersensitivity to the active substance, to murine proteins, or to any of the other excipients of rituximab.

11. Significant medical diseases or conditions, as assessed by the Investigators and Sponsor that would substantially increase the risk-benefit ratio of participating in the study. This includes but is not limited to acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, severely immunocompromised state, and congestive heart failure New York Heart Association (NYHA) Class II-IV.

12. History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements or give informed consent.

13. Pregnancy or active breastfeeding.

14. Additional exclusion criteria for DLBCL chemotherapy combination (magrolimab + R-GemOx) Phase 1b safety dose-escalation and expansion cohorts only:

-a. Undergone ASCT within a period of less than or equal to 3 months before signing informed consent.

-b. Prior treatment with gemcitabine and oxaliplatin. However, patients who relapse greater than or equal to 12 months after treatment with a gemcitabine and/or oxaliplatincontaining

regimen are allowed.

-c. Known hypersensitivity to gemcitabine, oxaliplatin, or other platinum compounds.

-d. Intolerance of gemcitabine, oxaliplatin, and/or rituximab as monotherapy or in combination due to unacceptable toxicities as determined by the treating Investigator.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Mark J. Roschewski, M.D.
National Cancer Institute (NCI)
(240) 760-6183

NCI Medical Oncology Referral Office
National Cancer Institute (NCI)

(240) 760-6050

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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